Max Planck Institute for Medical Research

At the Max Planck Institute for Medical Research, physicists, chemists and biologists create knowledge of long-term relevance to basic medical science. The institute has a unifying theme: observing and controlling the vastly complex macromolecular interactions in the context of cells - both in health and disease. The presently four departments contribute to this goal through their complementary expertise. They work on optical microscopy with nanometer resolution, on the design of chemical reporter molecules, on macromolecular structure determination and on cellular, materials and biophysical sciences. The institute has a distinguished history of fundamental breakthroughs, evidenced by six Nobel Prizes awarded to its researchers since its foundation.

The yearbook of the Max Planck Society illustrates the research carried out at our institutes. We selected a few reports from our 2017 yearbook to illustrate the variety and diversity of topics and projects.
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Life is motion and interaction with the environment. This is equally true of cells within an organism, but for cells to get from one place to another, they not only have to be able to move, they also have to interact with their environment. Joachim Spatz and his team at the Max Planck Institute for Medical Research in Heidelberg are studying how cells manage this. In his search for answers, the winner of the 2017 Leibniz Prize puts cells through their paces on catwalks and obstacle courses to test their adhesive properties.

The collective and correlated migration of cells as a group is a hallmark of tissue remodeling events. As such it is essential to both life-supporting processes, like wound repair and embryonic morphogenesis, as well as pathological processes, like cancer invasion. The Max Planck researchers have successfully decoded the physical and molecular mechanisms that regulate networking and orientation in groups of cells that move as one.
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The exchange of nitrogen between the atmosphere and organic matter is crucial for life on Earth. One major route for this cycle, discovered only in the 1990s, is the anammox pathway that is found in certain bacteria. It proceeds via hydrazine, a highly reactive substance used by humans as a rocket fuel. A study of the structure of the enzymes involved in making and handling hydrazine in the bacterial cell offers striking insights into the possibilities of an unconventional intracellular chemistry.
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Finding our way in our daily environment is essential for survival, but how do we do it? The answer to this question is relevant to understanding dementia. Mice are a useful experimental model here. A mouse receives a lot of information about its environment and must decide in every situation what information is most helpful and what is misleading. Nerve cells of the central region of the brain, the hippocampus, use NMDA receptors not to store information about the environment, but instead to recognize, judge and decide which items of information are most useful.
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There is an urgent need to be able to synthesize modified glycopeptide antibiotics quickly to keep up with the problem of bacterial resistance. On an industrial scale this is currently not possible, because the crucial steps of the natural antibiotic synthesis are too little understood. New detailed insights into these mechanisms offer the hope of simulating this process in the laboratory, to allow a variety of more substantially altered glycopeptide antibiotics to be produced in rapid response to developing bacterial resistance.

An animal’s ability to respond to stress can be the difference between life and death when it is faced with an unfamiliar or inhospitable environment. Dr. Soojin Ryu at the MPI for Medical Research uses larval zebrafish to investigate how stress modifies brain and behavior.
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Perception of visual motion is of fundamental importance in order to safely move around and to skillfully reach and grasp objects. When using visual input to control goal-directed motion, our brain makes a decision to select the object of greatest salience in the visual field in order to steer the eyes, the head and the hand towards it. Even the small zebrafish larva exhibits a complex goal-directed behavior thanks to its refined visual system. Research at the Max Planck Institute for Medical Research now reveals how motion stimuli are processed in the brain of this little hunter.

Toxin-Antitoxin (TA) systems are genetic elements that can be found in the genomes of nearly all bacteria. They encode for a toxin protein as well as its cognate antitoxin. When the antitoxin is degraded, the toxin is released and the host bacterium dies. Based on this mechanism, the epsilon/zeta TA-family not only helps pathogenic bacteria to stabilize resistance genes but also to increase their virulence. The discovery of the working principle of zeta toxins at the Max Planck Institute for Medical Research now allows to explain both of these phenomena.
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How sensory stimuli are processed by neural networks is a key question of neuroscience. Olfactory conditioning experiments in mice demonstrate that odour processing is fast and stimulus-dependent. Selective genetic perturbation of the inhibitory circuitry in the first relay station of olfactory processing, the olfactory bulb, altered such discrimination times, with increased inhibition accelerating and decreased inhibition slowing down odour discrimination. This illustrates that inhibition can fulfil a key role in sensory processing.
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Synaptogenesis and synaptic plasticity require interactions between pre- and postsynaptic components. The neuromuscular synapse as model and genetically manipulated mice were used to study the dynamics of acetylcholine receptors. Direct in vivo analysis shows how newly synthesized receptors are integrated into the existing synapse and how receptor stability changes when muscle is inactivated by innervation.
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Glutamate is the most prevalent neurotransmitter at excitatory synapses of our nervous system and thus indispensable for the activity and accomplishments of our brain. Genetic manipulations in the model organism mouse permit an evaluation of the role of synaptic key components activated by glutamate in spatial learning paradigms. A mouse mutant reveals that a particular synaptic component is essential for a sense of familiarity with a recently encountered spatial environment, and hence functions as a molecular building block in learning and memory.
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Our eyes receive a permanent stream of visual information, which needs to be interpreted promptly and correctly. To deal with this enormous amount of data, processing starts already in the back of our eye, in the retina, where important features of the viewed scene are extracted. To elucidate the organization and function of the underlying neuronal microcircuits is one of the research topics of the department of Biomedical Optics at the MPI for Medical Research in Heidelberg.
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Many organisms exhibit photoreceptors in order to adapt to changing light conditions. The photoreceptor family of phototropins and the only recently identified BLUF (sensor of blue light using FAD) photoreceptors control a number of interesting cellular processes depending on blue light signals. By quantum chemical and structural investigations, important insights into the mechanism of function of these light switches have been gathered at the Max Planck Institute for Medical Research.
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A dogma in the Neurosciences states that learning causes long-lasting changes in chemical synapses of the brain. The goal of the Department of Molecular Neurobiology at the MPI for Medical Research is to describe the function of key molecules for such changes. Most synapses in the brain are excitatory in nature and operate with the chemical transmitter L-glutamate, which when released upon an impulse from the sending part of the synapse (presynaptic specialization), diffuses across the synaptic cleft and binds to postsynaptically localized specific receptors. Binding of glutamate opens an inherent pore in the receptors, such that for a brief moment (several msec) positively charged ions (cations) flow into the nerve cell, shifting the cell from its resting state to an excited state by depolarizing its membrane potential. Genetic manipulation of glutamate receptors (GluRs) in the mouse alters synaptic function and may impair or – more rarely – enhance learning abilities. The following investigations highlight important functional aspects of glutamate receptors in spatial learning for which the hippocampus, a prominent brain structure, is essential, and also in olfactory learning in olfactory synapses. Moreover, the expression of functionally altered GluRs can evoke neurodegenerative diseases such as epilepsy and amyotrophic lateral sclerosis.
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In addition to neurons the brain contains several types of glial cells. While neurons are responsible for fast signal transmission and processing, the functional roles of glial cells have largely remained elusive, in part because methods to investigate these cells in the intact brain were lacking. The development of novel staining methods and in vivo application of two-photon fluorescence microscopy has now enabled to visualize glial cells with high spatial and temporal resolution in the intact neocortex and to study their behavior. Using this combined approach, wave-like oscillations of the intracellular calcium concentration were resolved in the network of astrocytes. These waves might be involved in long-range signaling in the neocortex. In addition, microglial cells, the defense cells of the brain, were found to be not at rest in the healthy brain; they continually survey the surrounding parenchyma with their motile processes showing an astonishingly high level of structural plasticity that far exceeds what is known from other cell types. Moreover, microglial cells took immediate protective actions upon rupture of a blood vessel by targeting and shielding the injured site with their processes. These new results highlight the importance of glial cells as fundamental elements of the brain, both under normal physiological conditions as well as following brain damage such as for example caused by a stroke.
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The goal of the Dept. for Biomedical Optics is the development of novel methods to better understand computation in the brain. There are two main lines of attack: measuring activity and reconstructing circuits. Fast information transmission in the brain is mediated mainly by neuronal processes, called axons, only which electrochemical excitation actively propagates. Along those axons we find in a more or less regular pattern special cellular organelles, which are able to connect to neighboring neuronal processes (dendrites) and thus allow the transmission of information to those cells.
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